P14922 (CYC8_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
General transcriptional corepressor CYC8

Alternative name(s):
Glucose repression mediator protein CYC8

Gene names

Name:	CYC8
Synonyms:	CRT8, SSN6
Ordered Locus Names:	YBR112C
ORF Names:	YBR0908

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	966 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as component of the CYC8-TUP1 corepressor complex which is involved in the repression of many genes in a wide variety of physiological processes including heme-regulated and catabolite repressed genes. May also be involved in the derepression of at least some target genes. The complex is recruited to target genes by interaction with DNA-bound transcriptional repressors, like MATALPHA2, MIG1, RFX1 and SKO1. The complex recruits histone deacetylases to produce a repressive chromatin structure, interacts with hypoacetylated N-terminal tails of histones H3 and H4 that have been programmed for repression by the action of histone deacetylases and interferes directly with the transcriptional machinery by associating with the RNA polymerase II mediator complex. Ref.11 Ref.12 Ref.14 Ref.18 Ref.19
Subunit structure	Associates with TUP1 to form the CYC8-TUP1 (or TUP1-SSN6) corepressor complex that is composed of 4 copies of TUP1 and one copy of CYC8. Interacts with MATALPHA2, CTI6, MIG1, TUP1, SUT1, RFX1, PGD1, HOS1, HOS2 AND RPD3. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17
Subcellular location	Nucleus.
Domain	The prion domain (PrD) is a Gln/Asn (Q/N)-rich domain, which is unstructured in its native, soluble form, and which forms a parallel in-register beta-sheet in its amyloid form By similarity. Ref.6
Miscellaneous	[OCT+] is the prion form of CYC8. [OCT+] is the result of a conformational change of the cellular CYC8 protein that becomes self-propagating and infectious. [OCT+] aggregates sequester soluble CYC8, resulting in increased levels of iso-2-cytochrome c, defects in sporulation and mating, higher levels of invertase derepression and increased flocculation, reminiscent of a partial loss of function of the CYC8-TUP1 corepressor complex. [OCT+] can be cured by GdnHCl and by inactivation of the molecular chaperone HSP104, which is required for [OCT+] propagation. It is speculated that prion properties of transcription factors may generate an optimized phenotypic heterogeneity that buffers yeast populations against diverse environmental insults (Ref.26). Present with 3890 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the CYC8/SSN6 family. Contains 10 TPR repeats.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Amyloid Nucleus
Domain	Repeat TPR repeat
Molecular function	Prion Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chromatin remodeling Inferred from genetic interaction PubMed 14739928. Source: SGD negative regulation of dipeptide transport by negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 18708352. Source: SGD negative regulation of transcription from RNA polymerase II promoter during mitosis Inferred from mutant phenotype PubMed 9560430. Source: SGD nucleosome positioning Inferred from direct assay PubMed 15116071. Source: SGD regulation of fatty acid biosynthetic process by regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 9280286. Source: SGD regulation of response to DNA damage stimulus Inferred from mutant phenotype Ref.10. Source: SGD regulation of transcription from RNA polymerase II promoter in response to osmotic stress Inferred from mutant phenotype PubMed 9858577. Source: SGD
Cellular_component	transcriptional repressor complex Inferred from direct assay PubMed 9111019. Source: SGD
Molecular_function	RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription Inferred from direct assay Ref.10. Source: SGD RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Inferred from direct assay PubMed 9867831. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HOS2	P53096	4	EBI-18215,EBI-8475
PGD1	P40356	3	EBI-18215,EBI-13268
RFX1	P48743	2	EBI-18215,EBI-15036
RPD3	P32561	6	EBI-18215,EBI-15864
TUP1	P16649	7	EBI-18215,EBI-19654

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 966	966	General transcriptional corepressor CYC8		PRO_0000106327
Regions
	Repeat	46 – 79	34	TPR 1
	Repeat	80 – 113	34	TPR 2
	Repeat	114 – 147	34	TPR 3
	Repeat	150 – 183	34	TPR 4
	Repeat	187 – 220	34	TPR 5
	Repeat	224 – 257	34	TPR 6
	Repeat	262 – 295	34	TPR 7
	Repeat	296 – 329	34	TPR 8
	Repeat	330 – 363	34	TPR 9
	Repeat	364 – 398	35	TPR 10
	Region	467 – 682	216	Prion domain (PrD)
	Compositional bias	15 – 30	16	Poly-Gln
Amino acid modifications
	Modified residue	429	1	Phosphoserine Ref.25
	Modified residue	475	1	Phosphothreonine Ref.25
	Modified residue	710	1	Phosphoserine Ref.23 Ref.25
	Modified residue	741	1	Phosphoserine Ref.24 Ref.25
	Modified residue	755	1	Phosphoserine Ref.25
	Modified residue	768	1	Phosphoserine Ref.25
	Modified residue	779	1	Phosphothreonine Ref.25
	Modified residue	780	1	Phosphoserine; by ATM or ATR Ref.24 Ref.25
	Modified residue	793	1	Phosphoserine Ref.25
	Modified residue	805	1	Phosphoserine Ref.21 Ref.25
	Modified residue	815	1	Phosphoserine Ref.22 Ref.24 Ref.25
	Modified residue	817	1	Phosphoserine Ref.22 Ref.25
	Modified residue	866	1	Phosphoserine Ref.25
	Modified residue	939	1	Phosphoserine Ref.25
	Modified residue	943	1	Phosphoserine Ref.22 Ref.25
Experimental info
	Sequence conflict	547	1	Q → K in AAA34545. Ref.1
	Sequence conflict	547	1	Q → K in AAA35103. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P14922 [UniParc]. Last modified October 5, 2010. Version 2. Checksum: FC2D0D0C1B181207	FASTA	966	107,202
	10 20 30 40 50 60 MNPGGEQTIM EQPAQQQQQQ QQQQQQQQQQ AAVPQQPLDP LTQSTAETWL SIASLAETLG 70 80 90 100 110 120 DGDRAAMAYD ATLQFNPSSA KALTSLAHLY RSRDMFQRAA ELYERALLVN PELSDVWATL 130 140 150 160 170 180 GHCYLMLDDL QRAYNAYQQA LYHLSNPNVP KLWHGIGILY DRYGSLDYAE EAFAKVLELD 190 200 210 220 230 240 PHFEKANEIY FRLGIIYKHQ GKWSQALECF RYILPQPPAP LQEWDIWFQL GSVLESMGEW 250 260 270 280 290 300 QGAKEAYEHV LAQNQHHAKV LQQLGCLYGM SNVQFYDPQK ALDYLLKSLE ADPSDATTWY 310 320 330 340 350 360 HLGRVHMIRT DYTAAYDAFQ QAVNRDSRNP IFWCSIGVLY YQISQYRDAL DAYTRAIRLN 370 380 390 400 410 420 PYISEVWYDL GTLYETCNNQ LSDALDAYKQ AARLDVNNVH IRERLEALTK QLENPGNINK 430 440 450 460 470 480 SNGAPTNASP APPPVILQPT LQPNDQGNPL NTRISAQSAN ATASMVQQQH PAQQTPINSS 490 500 510 520 530 540 ATMYSNGASP QLQAQAQAQA QAQAQAQAQA QAQAQAQAQA QAQAQAQAQA QAQAQAHAQA 550 560 570 580 590 600 QAQAQAQAQA QAQAQAQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQLQP LPRQQLQQKG 610 620 630 640 650 660 VSVQMLNPQQ GQPYITQPTV IQAHQLQPFS TQAMEHPQSS QLPPQQQQLQ SVQHPQQLQG 670 680 690 700 710 720 QPQAQAPQPL IQHNVEQNVL PQKRYMEGAI HTLVDAAVSS STHTENNTKS PRQPTHAIPT 730 740 750 760 770 780 QAPATGITNA EPQVKKQKLN SPNSNINKLV NTATSIEENA KSEVSNQSPA VVESNTNNTS 790 800 810 820 830 840 QEEKPVKANS IPSVIGAQEP PQEASPAEEA TKAASVSPST KPLNTEPESS SVQPTVSSES 850 860 870 880 890 900 STTKANDQST AETIELSTAT VPAEASPVED EVRQHSKEEN GTTEASAPST EEAEPAASRD 910 920 930 940 950 960 AEKQQDETAA TTITVIKPTL ETMETVKEEA KMREEEQTSQ EKSPQENTLP RENVVRQVEE DENYDD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the CYC8 gene mediating glucose repression in yeast." Trumbly R.J. Gene 73:97-111(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Molecular analysis of SSN6, a gene functionally related to the SNF1 protein kinase of Saccharomyces cerevisiae." Schultz J., Carlson M. Mol. Cell. Biol. 7:3637-3645(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Molecular analysis of yeast chromosome II between CMD1 and LYS2: the excision repair gene RAD16 located in this region belongs to a novel group of double-finger proteins." Mannhaupt G., Stucka R., Ehnle S., Vetter I., Feldmann H. Yeast 8:397-408(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[4]	"Complete DNA sequence of yeast chromosome II." Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C., Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M., Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M., Cziepluch C. , Demolis N., Delaveau T., Doignon F., Domdey H., Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D., Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N., Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J., Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C., Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P., Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y., Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F., Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E., Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M., Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B., Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L., Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M., Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S., Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K., Mewes H.-W., Kleine K. EMBO J. 13:5795-5809(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[6]	"A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis." Sikorski R.S., Boguski M.S., Goebl M., Hieter P.A. Cell 60:307-317(1990) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAINS TPR REPEATS.
[7]	"The tetratricopeptide repeats of Ssn6 interact with the homeo domain of alpha 2." Smith R.L., Redd M.J., Johnson A.D. Genes Dev. 9:2903-2910(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MATALPHA2.
[8]	"Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein." Treitel M.A., Carlson M. Proc. Natl. Acad. Sci. U.S.A. 92:3132-3136(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MIG1.
[9]	"The Cyc8 (Ssn6)-Tup1 corepressor complex is composed of one Cyc8 and four Tup1 subunits." Varanasi U.S., Klis M., Mikesell P.B., Trumbly R.J. Mol. Cell. Biol. 16:6707-6714(1996) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[10]	"The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor." Huang M., Zhou Z., Elledge S.J. Cell 94:595-605(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RFX1.
[11]	"Ssn6-Tup1 interacts with class I histone deacetylases required for repression." Watson A.D., Edmondson D.G., Bone J.R., Mukai Y., Yu Y., Du W., Stillman D.J., Roth S.Y. Genes Dev. 14:2737-2744(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TUP1; HOS2 AND RPD3, FUNCTION OF THE CYC8-TUP1 COMPLEX.
[12]	"Hrs1/Med3 is a Cyc8-Tup1 corepressor target in the RNA polymerase II holoenzyme." Papamichos-Chronakis M., Conlan R.S., Gounalaki N., Copf T., Tzamarias D. J. Biol. Chem. 275:8397-8403(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PGD1, FUNCTION OF THE CYC8-TUP1 COMPLEX.
[13]	"A sequence resembling a peroxisomal targeting sequence directs the interaction between the tetratricopeptide repeats of Ssn6 and the homeodomain of alpha 2." Smith R.L., Johnson A.D. Proc. Natl. Acad. Sci. U.S.A. 97:3901-3906(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MATALPHA2.
[14]	"Regulation of the Sko1 transcriptional repressor by the Hog1 MAP kinase in response to osmotic stress." Proft M., Pascual-Ahuir A., de Nadal E., Arino J., Serrano R., Posas F. EMBO J. 20:1123-1133(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE CYC8-TUP1 COMPLEX.
[15]	"SUT1p interaction with Cyc8p(Ssn6p) relieves hypoxic genes from Cyc8p-Tup1p repression in Saccharomyces cerevisiae." Regnacq M., Alimardani P., El Moudni B., Berges T. Mol. Microbiol. 40:1085-1096(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SUT1.
[16]	"Cti6, a PHD domain protein, bridges the Cyc8-Tup1 corepressor and the SAGA coactivator to overcome repression at GAL1." Papamichos-Chronakis M., Petrakis T., Ktistaki E., Topalidou I., Tzamarias D. Mol. Cell 9:1297-1305(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CTI6.
[17]	"Tup1-Ssn6 interacts with multiple class I histone deacetylases in vivo." Davie J.K., Edmondson D.G., Coco C.B., Dent S.Y. J. Biol. Chem. 278:50158-50162(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOS1; HOS2 AND RPD3.
[18]	"Histone-dependent association of Tup1-Ssn6 with repressed genes in vivo." Davie J.K., Trumbly R.J., Dent S.Y. Mol. Cell. Biol. 22:693-703(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE CYC8-TUP1 COREPRESSOR COMPLEX.
[19]	"Recruitment of Tup1-Ssn6 by yeast hypoxic genes and chromatin-independent exclusion of TATA binding protein." Mennella T.A., Klinkenberg L.G., Zitomer R.S. Eukaryot. Cell 2:1288-1303(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE CYC8-TUP1 COMPLEX.
[20]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[21]	"Quantitative phosphoproteomics applied to the yeast pheromone signaling pathway." Gruhler A., Olsen J.V., Mohammed S., Mortensen P., Faergeman N.J., Mann M., Jensen O.N. Mol. Cell. Proteomics 4:310-327(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-805, MASS SPECTROMETRY. Strain: YAL6B.
[22]	"Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae." Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., Elias J.E., Gygi S.P. J. Proteome Res. 6:1190-1197(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-815; SER-817 AND SER-943, MASS SPECTROMETRY. Strain: ADR376.
[23]	"Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry." Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L., Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F. Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-710, MASS SPECTROMETRY.
[24]	"Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Smolka M.B., Albuquerque C.P., Chen S.H., Zhou H. Proc. Natl. Acad. Sci. U.S.A. 104:10364-10369(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-741; SER-780 AND SER-815, MASS SPECTROMETRY.
[25]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-429; THR-475; SER-710; SER-741; SER-755; SER-768; THR-779; SER-780; SER-793; SER-805; SER-815; SER-817; SER-866; SER-939 AND SER-943, MASS SPECTROMETRY.
[26]	"The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion." Patel B.K., Gavin-Smyth J., Liebman S.W. Nat. Cell Biol. 11:344-349(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PRION FORMATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M23440 Genomic DNA. Translation: AAA34545.1. M17826 Genomic DNA. Translation: AAA35103.1. X66247 Genomic DNA. Translation: CAA46973.1. X78993 Genomic DNA. Translation: CAA55615.1. Z35981 Genomic DNA. Translation: CAA85069.1. BK006936 Genomic DNA. Translation: DAA07232.1.
PIR	S25365.
RefSeq	NP_009670.3. NM_001178460.3.
3D structure databases
ProteinModelPortal	P14922.
SMR	P14922. Positions 45-395.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-696N.
IntAct	P14922. 8 interactions.
MINT	MINT-579675.
STRING	4932.YBR112C.
Proteomic databases
PaxDb	P14922.
PeptideAtlas	P14922.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YBR112C; YBR112C; YBR112C.
GeneID	852410.
KEGG	sce:YBR112C. sce:YBR117C.
Organism-specific databases
SGD	S000000316. CYC8.
Phylogenomic databases
eggNOG	COG0457.
GeneTree	ENSGT00640000091592.
KO	K00615. K06665.
OrthoDB	EOG4KPXK4.
Gene expression databases
Genevestigator	P14922.
GermOnline	YBR112C. Saccharomyces cerevisiae.
Family and domain databases
Gene3D	1.25.40.10. 2 hits.
InterPro	IPR001440. TPR-1. IPR013026. TPR-contain_dom. IPR011990. TPR-like_helical. IPR019734. TPR_repeat. [Graphical view]
Pfam	PF00515. TPR_1. 6 hits. [Graphical view]
SMART	SM00028. TPR. 10 hits. [Graphical view]
PROSITE	PS50005. TPR. 9 hits. PS50293. TPR_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	971258.

Entry information

Entry name

CYC8_YEAST

Accession

Primary (citable) accession number: P14922
Secondary accession number(s): D6VQB2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	October 5, 2010
Last modified:	May 1, 2013
This is version 152 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program